title: NS3 protease from hepatitis C virus: biophysical studies on an intrinsically disordered protein domain.
abstract: The nonstructural protein 3 (NS3) from the hepatitis C virus (HCV) is responsible for processing the non-structural region of the viral precursor polyprotein in infected hepatic cells. NS3 protease activity, located at the N-terminal domain, is a zinc-dependent serine protease. A zinc ion, required for the hydrolytic activity, has been considered as a structural metal ion essential for the structural integrity of the protein. In addition, NS3 interacts with another cofactor, NS4A, an accessory viral protein that induces a conformational change enhancing the hydrolytic activity. Biophysical studies on the isolated protease domain, whose behavior is similar to that of the full-length protein (e.g., catalytic activity, allosteric mechanism and susceptibility to inhibitors), suggest that a considerable global conformational change in the protein is coupled to zinc binding. Zinc binding to NS3 protease can be considered as a folding event, an extreme case of induced-fit binding. Therefore, NS3 protease is an intrinsically (partially) disordered protein with a complex conformational landscape due to its inherent plasticity and to the interaction with its different effectors. Here we summarize the results from a detailed biophysical characterization of this enzyme and present new experimental data.
authors.affiliation: Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit BIFI-IQFR (CSIC), University of Zaragoza, Zaragoza 50018, Spain. oabifra@unizar.es.
authors.forename: Sonia
authors.initials: S
authors.lastname: Vega
authors.forename: Jose L
authors.initials: JL
authors.lastname: Neira
authors.forename: Carlos
authors.initials: C
authors.lastname: Marcuello
authors.forename: Anabel
authors.initials: A
authors.lastname: Lostao
authors.forename: Olga
authors.initials: O
authors.lastname: Abian
authors.forename: Adrian
authors.initials: A
authors.lastname: Velazquez-Campoy
mesh_terms: D016174:Hepacivirus / Q000201:enzymology*; D006801:Humans; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D017361:Viral Nonstructural Proteins; D015032:Zinc; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus